Expert Recaps Recent Developments in HER2+ Breast Cancer

The treatment of patients with HER2-positive breast cancer has evolved quite a bit in recent years; however, there is still more than can be achieved, explains Chau T. Dang, MD.

“HER2-positive breast cancer was a very difficult disease to treat and now we have so many options, including taxane with trastuzumab and pertuzumab in the first-line and T-DM1 in the second-line setting,” says Dang, a medical oncologist at Memorial Sloan Kettering Cancer Center. “But, what about beyond that?”

In an interview with OncLive, Dang discusses several recent trials investigating novel treatment approaches for patients with HER2-positive breast cancer. These include the PHEREXA trial, which explored the combination of trastuzumab and pertuzumab (Perjeta) in the second-line setting, and the ongoing NALA study, which is investigating neratinib plus capecitabine compared with lapatinib (Tykerb) and capecitabine in metastatic disease.

MYL-1401O, a biosimilar version of trastuzumab, also has potential to make a difference for patients with HER2-positive disease who may not have access to trastuzumab, adds Dang.

The drug recently demonstrated an overall response rate (ORR) of 69.6% among women who received MYL-1401O in combination with a taxane compared with a 64% ORR at 24 weeks for patients who received trastuzumab plus a taxane, demonstrating equivalency between the biosimilar and trastuzumab.

In the interview, Dang also explains the biggest challenges with HER2-positive breast cancer that need to be addressed and what she hopes to see achieved in the future.

OncLive: What did we learn from the PHEREXA trial?

Dang: The PHEREXA trial looked at the combination of trastuzumab and pertuzumab in the second-line setting. We know that dual-antibody therapy with chemotherapy is indicated for first-line, but we did not know if it had potential in second-line.

The PHEREXA study was for patients who were being treated in the second-line setting and progressed after a taxane- and trastuzumab-based treatment. The patients were randomized to receive capecitabine and trastuzumab or capecitabine, trastuzumab, and pertuzumab.

The primary endpoint of the study was progression-free survival (PFS) by independent assessment and a secondary endpoint included overall survival. Although it did show a numerical increase in PFS, it was not statistically significant; in essence, it was a negative study.

Interestingly, in terms of OS, there was a difference of 8 months for survival in favor of pertuzumab. However, I want to say this carefully because this trial was not powered to look at survival—but it did make us think that these antibodies have a greater effect on survival than PFS. We have seen that with trastuzumab and pertuzumab in the CLEOPATRA study where the benefit in OS was better than seen with PFS.

What we should take away from this study is that it was a valiant effort by investigators to look at that activity of capecitabine, trastuzumab, and pertuzumab in the second-line setting. However, because it was negative, T-DM1 remains to be the standard second-line option. We work very hard as physicians with patients to try and find better treatments. Certainly, though, T-DM1 is a still an excellent option.

Please discuss the significance of the emergence of trastuzumab biosimilars.

At the 2016 ASCO Annual Meeting, Dr Hope Rugo reported a study looking at [the biosimilar] MYL-1401O with a taxane versus trastuzumab with a taxane as first-line treatment for patients with HER2-positive metastatic breast cancer. It is, essentially, an equivalency trial, and she did show that this proposed biosimilar was equivalent to trastuzumab when both biologics were added to chemotherapy.

That is important to note because trastuzumab is not widely available worldwide. One of the main reasons is because of the cost. If we start seeing data of this biosimilar and hopefully others that may be available going forward, we will be able to treat more patients worldwide.

What other emerging therapies for HER2-breast cancer are you excited about?

Neratinib is being studied right now in a large phase III trial known as the NALA study, which is looking at neratinib plus capecitabine compared to lapatinib and capecitabine. This trial will allow us to see if neratinib, along with the standard chemotherapy, will beat its control and offer another option for our patients.